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Clinicopathological Features in Oral Cavity Squamous Cells Produced by podoplanin and Its Functional Role in Head and Neck Cancer Cell Lines

Head and neck cancer (HNC) makes up 6 ¢H of the cancer patients
in the world every year. This disease usually occurs in males and the
incidence is increasing year by year. According to statistical analysis,
HNC has less than 50 ¢H five-year survival rate. Therefore, the research
of HNC seems imminent so that may lead to the development of new
approaches of diagnosis and therapy.
Recent research had shown that expression of podoplanin caused
cellular proliferation, and may be associated with tumor invasion,
metastasis and malignant prognosis. Podoplanin, a mucin-type
transmembrane sialoglycoprotein, is highly expressed in lymphatic
endothelial cells but not expressed in vascular endothelial cells. The
purpose of this study was to determine the clinical and pathological
significance of podoplanin in oral squamous cell carcinoma (OSCC).
Therefore, we collected clinical specimen and associated patient history
of OSCC. Further, we used the human cell lines of HNSCC (Fadu, Hep2)
to investigate the molecular regulation of podoplanin.
Podoplanin expression was analyzed by RT-PCR and Western blot assay
firstly. As shown, podoplanin was found to be overexpressed in tumors compared with normal adjacent tissues. Further, immunohistochemical
analysis revealed the location of podoplanin expression in OSCC tissues.
The results showed that podoplanin had higher expression in T4 stage
tumor section than in normal adjacent tissues of OSCC samples, or in T1
stage. Here, podoplanin was highly expressed in the OSCC tumor cell
and lymphatics of stage T4 OSCC tissue. Furthermore, we found that
overexpression of podoplanin in OSCC patients was associated with
decreased five-years survival rate. In the univariate analysis, several
factors were statistically significantly associated with disease-specific
survival rate, including Tumor stage, Nodal stage, and podoplanin
expression. In the subsequent multivariate analysis, only Tumor stage and
Nodal stage showed a trend toward worse disease-specific survival. To
further investigate the regulatory mechanism of podoplanin and its
position of expression within the cell, immunofluorescence and
transfection were utilized to assay. The results showed that podoplanin
was expressed in the nuclear membrane of the Fadu and Hep2 cell lines,
and the PI3K/AKT signaling pathway was involved. We suggest that the
role of podoplanin in OSCC should be further investigated for potential
future treatment.

Identiferoai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0909108-102025
Date09 September 2008
CreatorsHsu, Yung-ting
ContributorsCho, Chung-Lung, Chao, David, Chien, Chin-Yen
PublisherNSYSU
Source SetsNSYSU Electronic Thesis and Dissertation Archive
LanguageCholon
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0909108-102025
Rightswithheld, Copyright information available at source archive

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